The LIR is currently prospectively studying the largest group of patients with the vasculitic syndromes in the world. On the basis of clinical, pathophysiologic, immunopathogenic and therapeutic results obtained over the past 15 years, we have designed a revised categorization scheme for the vasculitides which has now reached worldwide acceptance. We have developed and instituted aggressive chemotherapeutic regimens consisting of chronically administered cyclophosphamide together with alternate-day corticosteroids in several, formerly universally fatal diseases such as Wegener's granulomatosis. In this regard, over the past year we reported our long-term follow-up of 85 patients with Wegener's granulomatosis in which we demonstrated a 93% remission and cure rate. We have now applied these approaches with remarkable success to other of the vasculitic syndromes such as systemic vasculitis of the polyarteritis nodosa group, isolated central nervous system vasculitis, Takayasu's arteritis, and the acute vasculitis of Sjogren's syndrome. In addition, we studied the pathophysiology of lymphomatoid granulomatosis and have shown it to be a pre-lymphomatous condition which responds in its early stages to chemotherapeutic regimens used in the vasculitic syndromes. Patients who responded in the early stage did not go on to lymphoma and remained disease free over long-term follow-up. The patient populations studied in the vasculitis protocol have been utilized to precisely delineate aberrancies of lymphocyte activation and immunoregulation seen in these diseases. In addition, the precise effects of various therapeutic regimens, particularly corticosteroids and cytotoxic agents, on human lymphoid cells have been described. In this regard, we demonstrated the exquisite and selective sensitivity of certain phases of the B cell cycle to cyclophosphamide therapy, an observation which might help explain its efficacy in certain diseases characterized by hyperreactivity of B cell function.